No matter how badly a drug fails in Phase III, investigators and the companies that employ them often bend over backward to highlight any positive sign of efficacy, no matter how weak the signal. And GlaxoSmithKline's team at the American College of Cardiology meeting over the weekend was in full spin mode with their heart drug darapladib.
Once considered one of the most innovative and promising therapies in the Glaxo's ($GSK) pipeline, darapladib failed its first big Phase III test, losing a considerable amount of luster. On Sunday, investigators spelled out the data, which demonstrated clearly that darapladib looked a lot like a placebo when it came to the primary endpoint: time to the occurrence of the first major cardiac event for patients suffering from chronic coronary disease. There was no difference in mortality, but if you take a Panglossian perspective there was a slight, possible benefit in the number of major coronary events--9.3% in the darapladib group over 3.7 years and 10.3% for the placebo arm. The p value was 0.045, indicating "nominal" significance.
"Similar effects were observed for the composite of total coronary events, which occurred in 14.9% of patients on darapladib versus 16.1% on placebo," according to GSK's release.
That's not a silver lining. Perhaps it's more like a tin lining. But it was enough to warrant some hard spinning at the conference. And GlaxoSmithKline CEO Andrew Witty, while a little more reticent, helped support the upbeat reading of the results on Monday, telling Reuters that he saw "interesting potential signals" in the study, adding that the jury's still out on the drug's potential success.
"In the STABILITY study, the lack of effect on stroke was disappointing but not unexpected given the emerging epidemiology data," said Dr. Harvey White, who co-chaired the study, in a statement. "While the study didn't meet its primary endpoint, the effects of darapladib on the reduction of coronary events are of potential interest. These findings take us a step further towards defining which patients may benefit from treatment with darapladib."
White was even more pumped in an interview with Reuters.
"I'm convinced there is a signal here of efficacy," White told Reuters. The Phase III failure of darapladib against a sugar pill might have been influenced by the great care all the patients were given--which at least offers another lesson on the benefits of great care for heart patients--as well as the drug's specific inability to prevent strokes.
"There are some interesting potential signals in the secondary endpoints but an awful lot about what we've got here is going to depend on what we see on the second study," Witty told Reuters on Monday. "I think it is still an open question as to whether we've got something (that works) or not." Witty helped engineer the $3.6 billion acquisition in 2012 of Human Genome Sciences and darapladib.
GlaxoSmithKline has generally been quite open about its successes and failures, with a string of significant new drug approvals to its credit over the past year. Another Phase III study of darapladib is ongoing in patients treated within 30 days of a heart attack. So far, though, the hardcore optimists for this drug have apparently been reduced to a group of Glaxo insiders.
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